Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
  • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
  • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
  • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
  • C07D317/26—Radicals substituted by doubly bound oxygen or sulfur atoms or by two such atoms singly bound to the same carbon atom
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07J—STEROIDS
  • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C2603/00—Systems containing at least three condensed rings
  • C07C2603/02—Ortho- or ortho- and peri-condensed systems
  • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
  • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
  • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
  • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
  • C07C2603/16—Benz[e]indenes; Hydrogenated benz[e]indenes

Definitions

• novel compounds are useful as intermediates in the production of known steroids having useful physiological properties.
• An object of the invention is the obtention of novel hydroxylated tricyclic compounds useful as intermediates in the production of known steroids.
• a further object of the present invention is the development of a process for the obtention of 13fl-R-4,5-sec0-A gonene-3,5-diones of the formula 3,646,151 Patented Feb.
• R represents an alkyl having 1 to 4 carbon atoms and.A represents a member selected from the group consisting of which comprises the steps of (a) causing the double bond to migrate from the 9,10 position to the 9,11 position of a 3-keta1 of a 13fl-R-4,5-seco-A -gonene-3,S-dione of the formula ketal 0 wherein R represents an alkyl having 1 to 4 carbon atoms and A represents a member selected from the group consisting of by the action of a basic isomerization agent, followed by the action of an acid, (b) oxidizing the resultant 3-ketal of a 13B-R-4,5-scco-A -gonene-3,5-dione of the formula ketel wherein R and A have the above-assigned meanings, by the action of a gas containing oxygen, in a basic medium, (c) subjecting the resultant 3-keta1 of an 11 fi-hydroperoxy- 13fi-R-4,5
• R and A have the above-assigned meanings, by the action of a hydrolyzing acid, and (e) recovering said 13B-R-4,5-seco-A -gonene-3,5-diones.
• the invention relates to 13,6-R-4,5-seco-A -gonene-3,5- diones of the Formula I wherein, here and in the following, R represents an alkyl having 1 to 4 carbon atoms, either branched or straight chain, Y represents a hydroxyl and Z represents a hydrogen or Z and Y together represent a ketonic oxygen.
• the compounds of the general Formula I are useful as intermediates for the synthesis of steroids and steroidal derivatives. Their use in steroid synthesis allows the obtention in an advantageous fashion of numerous known steroids and steroidal derivatives having useful physiological properties by an unobvious new method of synthesis.
• the new compounds of the general Formula I are thus useful as intermediates in the synthesis of diverse steroidal compounds such as the l3fi-R-A -gonene-llfl,l7 3-diol-3- ones, the 13B-R-A -gonadiene-1 15,1713-diol-3-ones, the 135 R A -gonadiene-1lB-ol-3,17-diones, the l3B-R- A -gonatriene-175-01-3-ones and other steroidal derivatives of known interest.
• diverse steroidal compounds such as the l3fi-R-A -gonene-llfl,l7 3-diol-3- ones, the 13B-R-A -gonadiene-1 15,1713-diol-3-ones, the 135 R A -gonadiene-1lB-ol-3,17-diones, the l3B-R- A -gonatriene-175-01-3-
• the process of the invention can be further characterized by the methods of execution indicated below.
• the basic isomerization agent utilized in step 1 to act on the 3-ketal of a is a strong base such as an alkali metal tertiary-loweralkanolate, an alkali metal amide or an alkali metal acetylide, preferably a potassium tert.-amylate or tert.- butylate.
• aliphatic tertiary amines preferably the trilower alkylamines such as triethylamine; the cyclic tertiary amines such as pyridine and its homologs; and the organic derivatives of quaternary ammonium such as the benzyl-tri-loweralkyl ammonium halides, for example,
• a gas containing oxygen is effected conveniently in the presence of a lower alkanol such as ethanol or methanol or in the presence of an N,N-di-lower-alkyl lower-alkanoylamide such as dimethylformamide, or in a mixture of these, at about room temperature.
• a lower alkanol such as ethanol or methanol
• an N,N-di-lower-alkyl lower-alkanoylamide such as dimethylformamide
• a phosphite is chosen as the reducing agent, such as a tri-lower-alkyl phosphite, for example, trimethylphosphite or triethylphosphite.
• An alkali metal iodide such as potassium iodide, in the presence of a lower alkanoic acid, such as acetic acid, can also be utilized, or also other reducing agents can be utilized.
• the reduction reaction is preferably conducted in the presence of the solvent uti lized in the preceding oxidization step at temperatures up to the reflux temperature.
• the excess of the reducing agent is destroyed by an oxidizing agent such as hydrogen peroxide before the resultant compound is re covered.
• the acid hydrolysis step is conveniently efliected in the presence of one or several organic solvents such as a lower alkanol, for example, methanol or ethanol, or an aromatic hydrocarbon solvent such as benzene or toluene. Small amounts of water are conveniently utilized and the hydrolysis is conducted at elevated temperatures up to the reflux temperature.
• organic solvents such as a lower alkanol, for example, methanol or ethanol, or an aromatic hydrocarbon solvent such as benzene or toluene.
• the 3-ketal of a is preferably a 3-lower alkylenedioxy ketal such as 3,3- ethylenedioxy.
• the 3,3-ethylenedioxy-13fi-R-4,5-seco-A gonene-17B-ol-5-ones 0112-0 (II, with ketal: Y OH, 2:11
• the new compounds of the general Formula I are useful as intermediates in the synthesis of diverse monoenic, dienic or trienic steroid derivatives and other steroids of known interest.
• 13B-R-4,5-seco-A -gonene-11B,17;8-diol-3,5-dione is subjected to a catalytic hydrogenation, then the resultant 6 13p-R-4,5-seco-gonane-l1B,17,8-diol-3,5-dione is cyclized by the action of an acidic or basic cyclization agent.
• the corresponding 13,8-R-A -gonene-113,17fl-diol-3-one is obtained.
• the catalytic hydrogenation is conveniently effected with the aid of palladium hydroxide.
• This catalytic hydrogenation supplies, in addition to 13 3 R 4,5-seco-(9a,10 8)-gonane-11 8,17B-diol-3,5-dione, another isomer, the 13,8 R 4,5-seco-(9B,10a)-gonane- 11fl,17;3-diol-3,5-dione.
• the two isomers are separated due to their differences of solubility in a solvent or a mixture of solvents conveniently chosen, or by chromatography.
• the basic agent utilized in order to effect the cyclization of the 13fl-R-4,5-seco-gonane-llfi,17fl-diol-3,5-dione is, for example, an alkali metal hydroxide such as sodium or potassium hydroxide while operating in the presence of a lower alkanol such as methanol.
• the acidic agent utilized, if desired, in order to effect the same cyclization is, for example, hydrochloric acid, while operating in an acetic acid media.
• 13/3-R-4,S-seco-A -gonene-11B,17 8-diol-3,5-dione is cyclized by the action of a basic isomerization agent.
• the resultant 13;8-R-A -gonadiene-1 l fl,17[i-diol-3-one, is isomerized, if desired, by heating in the presence of a catalyst to obtain the corresponding 13fi-R-A -gonatriene- 3,113,17fl-triol.
• the basic agent utilized in order to effect the cyclization of the 13fi-R-4,5-sec0-A -gonene-11/3,17fl-diol-3,5-dione is, for example, an alkali metal hydroxide, such as sodium or potassium, while operating in a lower alkanol such as methanol.
• the isomerization catalyst utilized in order to effect isomerization of the 13B-R-A -gonadiene-115,17fl-diol-3- one is particularly palladium hydroxide. This isomerization is conveniently eflected by heating in a lower alkanol in the presence of a weak base such as magnesia.
• 11B-hydroxy-13fi-R-1T 4,5-seco-A-gonene-3,5-d1one is cyclized in a basic media.
• the resultant is dehydrated by the action of an acidic agent.
• the corresponding Y 13B-R-l7 --A --"-g0natr1ene-3bne is obtained.
• the basic agent utilized in order to effect the cyclization of the /Y 11fl-hydroxy-13fl-R-1Z -4,5-sec0-A -g0nene-3,5-dione is, for example, an alkali metal hydroxide, such as sodium or potassium hydroxide, while operating in a lower alkanol, such as methanol.
• the acidic agent utilized in order to effect the dehydration of the resultant /Y 1313-11-17 -A -gonadiene-llB-olfi-one is a strong acid, preferably a strong mineral acid such as perchloric acid, in solution in an organic solvent or mixture of organic solvents, such as methylene chloride and acetonitrile.
• the dehydrating agent can also be concentrated sulfuric acid and then, this dehydration is effected in the presence of an organic solvent, such as methylene chloride or ether, in a short time of the order of 3 to 15 minutes and at a temperature between C. and -10 C.
• reaction mixture was agitated at room temperature for a period of 5 hours, then the reaction mixture was poured into a mixture of 600 cc. of a 3% aqueous solution of boric acid and ice.
• the pH of the reaction media was about 8.5.
• the precipitate formed was extracted with methylene chloride.
• the methylene chloride solution was washed with water, dried, and concentrated to dryness. 16.2 gm. of raw 3,3-ethylenedioxy-4,5- seco-A -estrene-17B-ol-5-one was obtained, which was utilized as such for the next step.
• Step B 3,3 ethylenedioxy llfi hydroperoxy 4,5- seco A estrene-l7fi-ol-5-one.--16.2 gm. of raw 3,3- ethylenedioxy 4,5-seco-A -estrene-1713-ol-5-one were dissolved in 150 cc. of ethanol containing 1% of triethylamine. The solution was agitated under an atmosphere of oxygen at room temperature during 24 hours. It absorbed about 500 cc. of oxygen. The 3,3-ethylenedioxy- 11fl-hydroperoxy-4,5-seco-A -estrene l7/3-oI-5-one thus obtained was utilized as such in solution for the next stage.
• Step C 3,3 ethylenedioxy 4,5 seco-M-estrene-llfi, 17;8-diol-5-one.6.6 cc. of triethyl phosphite were introduced into the solution of 3,3-ethylenedioxy-llB-hydroperoxy 4,5-seco-A -estrene-17B-ol-5-one obtained in the preceding step (and derived from 15 gm. of 3,3- ethylenedioxy 4,5-seco-A -estrene-17fi-ol-5-one). The reaction mixture was heated to reflux and maintained there for a period of one hour. Then the reaction mixture was poured into a mixture of 30 cc.
• Step D 4,5-seco-A estrene-ll,B,l7fl-diol-3,5-dione.
• reaction mixture was cooled and made alkaline by the addition of an aqueus solution of sodium bicarbonate.
• the organic phase was separated by decantation.
• the aqueous phase was extracted with methylene chloride.
• the organic phases were combined, washed with water, and dried.
• Animal carbon black was added to the dried organic phases, and the mixture was agitated.
• the carbon black was eliminated by filtration and the solution was concentrated to dryness.
• the residue was dissolved in methylene chloride.
• the methylene chloride solution was passed through a column of magnesium silicate, and the solution obtained was concentrated to dryness.
• Step B 3,3 ethylenedioxy 11 8 hydroperoxy ethyl 4,5-seco-A -gonene-17/3-ol-5-one.--4 gm. of 3,3- ethylenedioxy 13,3 ethyl 4,5-seco-A -gonene17,8- ol-S-one (derived from 3.85 gm. of 3,3-ethylenedioxy- 135 ethyl 4,5-seco-A -gonene-17/3-ol-5-one) were dissolved in 40 cc. of ethanol containing 1% of triethylarnine. The solution was then agitated in an atmosphere of oxygen for 15 hours at room temperature. About 230 cc. of oxygen were thus absorbed. The 3,3-ethylenedioxy- 11B hydroperoxy 13B ethyl 4,5 seco A gonenel7/3-ol-5-one thus obtained was utilized as such in solution for the next step.
• Step C 3,3-ethylenedioxy 135 ethyl 4,5 sew-A gonene-ll5,175-diol--one.2.4 cc. of triethyl phosphite were introduced into the solution of 3,3-ethylenedioxy- 115-hydroperoxy 135 ethyl 4,5 seco-A -gonene-175- ol-5-one (derived from 3.85 gm. of 3,3-ethylenedioxy- 135-ethyl 4,5 seco-d -gonene-175-ol-5-one). The reaction mixture was agitated for one hour at room temperature.
• Fraction (B) was utilized as such for the following step.
• Step D 135-ethy1- 4,5 seco-d -gonene 115,175-diol- 3,5-dione.--1.4 cc. of water, 1.4 gm. of citric acid, and then 2.45 gm. of 3,S-ethylenedioxy-135-ethyl-4,5-seco-A gonene-l15,l75-diol5-one, the fraction (B) obtained in the preceding step, were introduced into 20 cc. of benzene in an atmosphere of nitrogen. The reaction mixture was heated to reflux and maintained at reflux for a period of one hour. Thereafter the reaction mixture was cooled, and water was added to it with agitation. The organic phase was separated by decantation.
• the aqueous phase was extracted with methylene chloride.
• the organic phases were combined, Washed with water, with an aqueous solu tion of sodium bicarbonate, and then with water.
• the organic solution was then dried, and animal carbon black was added thereto with agitation. The carbon black was eliminated by filtration, and the organic solution was concentrated to dryness.
• Example 3 .4,5 -seco-A -estrene-1 15-o1-3,5,17-trione Step A: 3,3-ethylenedioxy 4,5 seco-A -estrene-5,17- dione.10 gm. of 3,3-ethylenedioxy 4,5 seco-A -estrene- 175-ol-5-one (product obtained by the application of the process of US. Pat. 3,413,314) were introduced into cc. of acetone, and the mixture was agitated at room temperature until dissolution occurred. Thereafter, the reaction mixture was cooled to 10 C. and 7.8 cc. of a 4.6 N solution of a sulfochromic acid mixture was added.
• Step B 3,3-ethylenedioxy 4,5 seco-A -estrene-5, 17-dione.-91.5 gm. of 3,3-ethylenedioxy 4,5 seco-A estrene-5,17-dione and 90 gm. of potassium tert.-butylate were introduced, under an inert atmosphere, into 460 cc. of dimethylsulfoxide. Next, the reaction mixture was agitated at room temperature for 5 hours, then poured into a mixture of 3.66 liters of water and ice and 3.66 liters of a 3% aqueous solution of boric acid. The precipitate formed was extracted with methylene chloride. The methylene chloride solution was washed with water and dried. 2.35 liters of a solution of 3,3-ethylenedioxy-4,5- seco-A -estrene-5,l7-dione in methylene chloride were obtained, which solution was utilized as such for the next step of the synthesis.
• Step C 3,3-ethyle-nedioxy hydroperoxy-4,5-seco- A -estrene-5,17-dione.915 cc. of ethanol containing 1% of triethylamine were added to the solution obtained from the preceding step. A stream of oxygen was then passed through the solution under agitation overnight. A solution of 3,3-ethylenedioxy 115 hydroperoxy-4,5-seco-A -estrene-5,17-dione in methylene chloride was obtained, which was utilized as such for the next step.
• Step D 3,3-ethylenedioxy 4,5 seco-A -estrene-115- ol-5,17-dione.
• the solution of 3,3-ethylenedioxy-115-hydroperoxy-4,5-seco-A -estrene-5,17-dione obtained in the preceding step was heated under agitation and in an atmosphere of nitrogen, to the point where distillation of methylene chloride commenced. Then 47.5 cc. of triethyl phosphite were introduced into the warm mixture. The heating was continued for a period of one hour. Thereafter, the mixture was cooled to room temperature and poured into a mixture of 265 liters of water and ice and 392 cc. of a 30% hydrogen peroxide solution.
• Step E 4,5-seco-A -estrene 115 ol-3,5,17-trione.- 96 gm. of 3,3-ethylenedioxy-4,5-seco A estrene-115-ol- 5,17-dione were introduced into 960 cc. of benzene. Then 96 cc. of water and 96 cc. of citric acid were added to the mixture under agitation and under an atmosphere of nitrogen. The reaction mixture was heated to reflux for a period of one hour, cooled, and the aqueous phase was decanted. The aqueous phase was extracted with benzene. The organic phases were combined, and washed with a saturated solution of sodium bicarbonate, and then with water until the wash waters were neutral.
• Step B 3,3-ethylenedioxy 13B ethyl-4,5-seco-A gonene-5,l7-dione.-29.5 gm. of 3,3-ethylenedioxy-l3 8- ethyl-4,5-seco-A -gonene-5,17-dione, then 27 gm. of potassium tert.-butylate were introduced under an inert atmosphere into 270 cc. of dimethylsulfoxide. The mixture was agitated at room temperature for 5 hours and then poured into a mixture of 1,080 cc. of water and ice and 1,080 cc. of a 3% boric acid solution. The mixture was agitated for minutes and extracted with methylene chloride.
• Step C 3,3 ethylenedioxy-l lB-hydroperoxy-lIto-ethyl- 4,5-seco A -gonene-5,17-dione.270 cc. of ethanol containing 1% of triethylamine were added to the solution obtained in the preceding step. Then a stream of oxygen was passed through the reaction mixture under agitation overnight. A solution of 3,3-ethylenedioxy-1lfi-hydroperoxy-13;8-ethy1-4,5-seco-A -gonene-5,17-dione was obtained, which was utilized as such for the following step.
• Step D 3,3 ethylenedioxy 13 3 ethyl-4,5-seco-A gonene-l1B-ol-5,17-dione.
• the solution of 3,3-ethylene dioxy-llfl hydroperoxy-l3 8 ethyl 4,5-seco-A -gonene- 5,17-dionc was heated under agitation and under an atmosphere of nitrogen, until distillation commenced. Then 9 cc. of triethyl phosphite were added thereto. The methylene chloride was distilled. Then the reaction mixture was heated to reflux for a period of one hour under agitation.
• the mixture was cooled to room temperature, then poured into a mixture of 1.5 liters of water and ice and 50 cc. of a 30% hydrogen peroxide solution. The mixture was agitated for 15 minutes. Then the aqueous phase was extracted with methylene chloride. The organic phases were washed with water, then dried. The solution was distilled to dryness.
• Step E 13/3 ethyl 4,5-seco-A -gonene-l15-01-3517- trione.-34 gm. of 3,3-ethylenedioxy-l3/3-ethyl-4,5-seco A -gonene-11fi-ol-5,17-dione, 27 gm. of cittric acid, and 27 cc. of water were introduced under an atmosphere of nitrogen into 270 cc. of benzene. The mixture was heated to reflux for a period of one hour and thereafter cooled to room temperature. 600 cc. of a saturated aqueous solution of sodium bicarbonate were added thereto and the aqueous phase was decanted. The aqueous phase was extracted with methylene chloride.
• Step '13 A -estrene 115,175 diol 3 one.50.5 gm. of raw 4,5-seco-estrane 115,175 diol 3,5 dione, obtained in Step A, was introduced under an atmosphere of nitrogen into 1010 cc. of a methanolic solution of potassium hydroxide containing 0.45 gm. of potassium hydroxide per 100 cc. The reaction mixture was heated to reflux and maintained at reflux for a period of 2 hours. Thereafter, the mixture was cooled to 20 C. and acidified to a pH of 5.5 by the addition of acetic acid. Water was added to the reaction mixture, and the methanol was eliminated by distillation under reduced pressure. The precipitate formed was vacuum filtered and dried.
• Step B (95,10a) A estrene 115, 175 diol 3- one.-5 gm. of (95,101) 4,5 seco-estrane 115,175- diol-3,5-dione were introduced under an atmosphere of nitrogen into 100 cc. of a methanolic solution of potassium hydroxide containing 0.45 gm. of potassium hydroxide per 100 cc. The solution was heated to reflux and maintained there for a period of 2 hours. The reaction solution was then cooled to 20 C. and brought to a pH of 5.5 by the addition of acetic acid. Water was then added thereto, and the methanol was eliminated by distillation under reduced pressure. The precipitate max. at 292 my.
• Step B 135 -ethyl-A -gonene-115,175-diol-3-one.3.8 gm. of 135 ethyl-4,5-seco-gonane-115,175-diol-3,5-dione were introduced into 76 cc. of a methanolic solution of potassium hydroxide containing 0.5 gm. of potassium hydroxide per 100 cc., under an atmosphere of nitrogen. The mixture was heated to reflux, and the reflux was maintained for a period of 2 hours. Thereafter, the reaction mixture was cooled and acidified by the addition of a dilute aqueous solution of acetic acid. The methanol was eliminated by distillation under reduced pressure, and the reaction mixture was cooled. The crystals obtained were vacuum filtered, washed and dried. 3.28 gm. of 135- ethyl-A -gonene-115,175-diol-3-one were obtained, having a melting point of 213 C.
• Example 8.-A -estratriene-17/3-ol-3-one Step A: A -estradiene-l1B,l7 B-diol-3-one.--3 gm. of 4,5-seco-A -estrene-1 15,17,8-diol-3 ,S-dione were introduced under an atmosphere of nitrogen into 30 cc. of a methanolic solution of potassium hydroxide containing 0.45 gm. of potassium hydroxide per 100 cc. The reaction mixture was heated to reflux and maintained there for a period of 6 hours. Thereafter, the reaction mixture was cooled to -+10 C. and neutralized by the addition of acetic acid. The solvent was eliminated by distillation.
• Step B A -estratriene-17,6diol-3-one were introduced in an atmosphere of nitrogen into 60 cc. of methylene chloride. The mixture was cooled to 5 C. and cc. of a 66 B. aqueous solution of sulfuric acid, then 30 cc. of ethyl ether were introduced into the solution. The reaction mixture was agitated vigorously for 5 min utes (starting from the moment of the introduction of the sulfuric acid) while cooling in order to bring the temperature to and maintaining the same at 0 C. The reaction mixture was then poured into a mixture of water and ice. The organic phase was separated by decantation. The aqueous phase was extracted with methylene chloride.
• the methylene chloride extracts and the principal organic phase were combined.
• the organic solution obtained was washed by an aqueous solution of sodium bicarbonate and then with water, dried and concentrated to dryness.
• the residue was dissolved in methylene chloride.
• the methylene chloride solution was passed through a column of magnesium silicate and eluted with methylene chloride.
• the eluate was concentrated to a small volume.
• the residue was crystallized from isopropyl ether. 1.73 gm. of A -estratriene-17B-ol-3-one was obtained, having a melting point of 182 C.
• Step B 13B-ethyl-A -gonatriene-1713-ol-3-one.- 3 gm. of l3B-ethyl-A -gonadiene-1113,17fi-diol-3-one were introduced, under an atmosphere of nitrogen and while agitating in order to homogenize the mixture and while maintaining the temperature of the reaction mixture at +15 C., into a mixture of 7.5 cc. of methylene chloride and 22.5 cc. of an aqueous 66 B. solution of sulfuric acid. At the end of 6 minutes, the reaction mixture was poured on ice. The methylene chloride phase was separated by decantation. The aqueous phase was extracted with methylene chloride.
• This compound is identical to 13fi-ethyl-A -gonatriene-l76-ol-3-one obtained by another method according to Belgian Patent No. 679,368.
• Example l0.A -estradiene-l 1B-o1-3 ,17-dione 2.3 gm. of 4,5-seco-A -estrene-llB-ol-3,5,l7-trione were introduced into 23 cc. of a methanolic potassium hydroxide solution (4 gm. per liter).
• the reaction mixture was heated to reflux under agitation and under an atmosphere of nitrogen for a period of 6 hours. Thereafter, the reaction mixture was cooled to room temperature and 1 cc. of a 10% acetic acid solution in methanol was added thereto. The reaction mixture was distilled to dryness under vacuum. The residue was dissolved in 10 cc.
• Example 1 l.1 3B-ethyl-A -gonadiene-11,B-ol-3,17-dione 30 gm. of l3B-ethyl-4,5-seco-A -gonene-11,8-ol-3,5,17- trione were introduced into 270 cc. of a methanolic potassium hydroxide solution (4.9 gm. per liter). The reaction mixture was heated to reflux under agitation and an atmosphere of nitrogen for a period of one hour. Thereafter, the reaction mixture was cooled to 20 C. and brought to a pH of between 5 and 6 by the addition of acetic acid. Then, the reaction mixture was diluted with 500 cc. of water.
• a methanolic potassium hydroxide solution 4.9 gm. per liter
• the aqueous phase was extracted with methylene chloride.
• the combined organic phases were washed with water, dried, and treated with animal carbon black.
• the organic phase was then filtered under vacuum, washed with methylene chloride, then distilled to dryness under vacuum.
• the residue was treated with isopropyl ether and with ether, then dissolved in 120 cc. of ethyl acetate, to which 100 cc. of isopropyl ether was slowly added.
• the mixture was agitated for one hour at 20 C. and filtered unuder vacuum.
• the "residue was triturated with isopropyl ether and dried under vacuum. 5.6 gm.
• R and A have the above-assigned meanings, by the action of a gas containing oxygen, in a basic media selected from the group consisting of tri-lower-alkylamines, tertiary cyclic amines and organic quaternary ammonium compounds, (c) subjecting the resultant 3- ketal of an 1lfi-hydroperoxy-13B-R-4,5-seco-A -gonene- 3,5-dione of the formula ketel wherein R and A have the above-assigned meanings, to the action of a reducing agent selected from the group consisting of tri-lower alkyl phosphites and alkali metal iodides in the presence of lower alkanoic acids, (d) hydrolyzing the resultant 3-ketal of an 1118-hydroxy-13B- R-4,5-seco-A -gonene-3,5-dione of the formula HO R ketel wherein R and A have the above-assigned meanings, by the action of
• step (a) wherein said isomerization step is effected in an organic solvent.
• organic solvent is selected from the group consisting of dimethylsulfoxide, dimethylformamide and the dimethyl ether of diethylene glycol.
• step (b) wherein said oxidization in a basic media is effected in the presence of a solvent selected from the group consisting of lower alkanols, N,N-di-lower alkyl lower-alkanoyl amides and mixtures of the two.

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Cited By (1)

• 1968
  • 1968-01-26 FR FR137630A patent/FR1574693A/fr not_active Expired
• 1969
  • 1969-01-20 IL IL31449A patent/IL31449A/xx unknown
  • 1969-01-23 CH CH100069A patent/CH505810A/fr not_active IP Right Cessation
  • 1969-01-23 US US793554*A patent/US3646151A/en not_active Expired - Lifetime
  • 1969-01-24 DK DK38869AA patent/DK138846B/da not_active IP Right Cessation
  • 1969-01-24 GB GB1252044D patent/GB1252044A/en not_active Expired
  • 1969-01-24 GB GB1252042D patent/GB1252042A/en not_active Expired
  • 1969-01-24 GB GB1252043D patent/GB1252043A/en not_active Expired
  • 1969-01-24 NL NL6901248A patent/NL6901248A/xx unknown
  • 1969-01-24 CA CA041,142A patent/CA983941A/en not_active Expired
  • 1969-01-27 JP JP44005365A patent/JPS5016357B1/ja active Pending
• 1974
  • 1974-11-18 JP JP49132106A patent/JPS5120509B1/ja active Pending
  • 1974-11-18 JP JP49132107A patent/JPS511713B1/ja active Pending

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